The overall aim of this application is to characterize the mechanism(s) regulating aldose reductase (AR2,EC1.1.1.21) gene expression in cells from tissues involved in the complications of diabetes, and to determine the basis for abnormal constitutive over-expression of AR2 by a line of human retinal pigment epithelial (RPE) cells. The rationale for this proposal rests on the postulated role of AR2 in the genesis of the chronic complications of diabetes, and the growing evidence that AR2 participates in, and is modulated by, physiological osmoregulation.